title: The VarS/VarA two-component system modulates the activity of the Vibrio cholerae quorum-sensing transcriptional regulator HapR.
abstract: The human pathogen Vibrio cholerae uses quorum sensing to regulate the expression of a number of phenotypes, including virulence factor production, in response to changes in cell density. It produces small molecules called autoinducers that increase in concentration as cell density increases, and these autoinducers bind to membrane sensors once they reach a certain threshold. This binding leads to signalling through a downstream phosphorelay pathway to alter the expression of the transcriptional regulator HapR. Previously, it was shown that the VarS/VarA two-component system acts on a component of the phosphorelay pathway upstream of HapR to regulate HapR expression levels. Here, we show that in addition to this mechanism of regulation, VarS and VarA also indirectly modulate HapR protein activity. This modulation is mediated by the small RNA CsrB but is independent of the known quorum-sensing system that links the autoinducers to HapR. Thus, the VarS/VarA two-component system intersects with the quorum-sensing network at two levels. In both cases, the effect of VarS and VarA on quorum sensing is dependent on the Csr small RNAs, which regulate carbon metabolism, suggesting that V. cholerae may integrate nutrient status and cell density sensory inputs to tailor its gene expression profile more precisely to surrounding conditions.
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Tsou
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D004251:DNA Transposable Elements / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D053038:Quorum Sensing / Q000235:genetics* / Q000502:physiology; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014734:Vibrio cholerae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C107123:CsrB RNA, E coli; D003470:Culture Media; D004251:DNA Transposable Elements; C091100:GacA protein, Bacteria; D047908:Intracellular Signaling Peptides and Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D015534:Trans-Activators; D011494:Protein Kinases; C560406:VarS protein, Vibrio cholerae